GLS2 and glioblastoma: We have shown previously that CB-839 may causes 3-MA, 3meLys and also 5-methyl cytosine levels to increase in GBM cells, which was thought to be due to imbalanced levels of AKG and succinate, implying AKG dioxygenases [35] GLS2 did not cause relative imbalance between AKG and succinate, so the potential effect of GLS2 on overall methylation levels is thought to be mediated by increased SAM levels, which is a critical methyl donor for methylation reactions [63].